The Intestine in Acute and Long COVID: Pathophysiological Insights and Key Lessons

Abstract

Post-Acute Sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, represents a significant and complex health challenge with a wide range of symptoms affecting multiple organ systems. This review examines the emerging evidence suggesting a critical role of the gut and gut-brain axis in the pathophysiology of Long COVID. It explores how changes in the gut microbiome, disruption of gut barrier integrity, and the persistence of SARS-CoV-2 antigens within the gastrointestinal tract may contribute to the prolonged and varied symptoms seen in Long COVID, including chronic inflammation and neuropsychiatric disturbances. The review also summarizes key insights gained about Long COVID, highlighting its multifactorial nature, which involves immune dysregulation, microvascular damage, and autonomic nervous system dysfunction, with the gut playing a central role in these processes. While progress has been made in understanding these mechanisms, current evidence remains inconclusive. The challenges of establishing causality, standardizing research methodologies, and addressing individual variations in the microbiome are discussed, emphasizing the need for further longitudinal studies and more comprehensive approaches to enhance our understanding of these complex interactions. This review underscores the importance of personalized approaches in developing effective diagnostic and therapeutic strategies for Long COVID, while also acknowledging the significant gaps in our current understanding. Future research should aim to further unravel the complex interplay between the gut and Long COVID, ultimately improving outcomes for those affected by this condition.

Keywords: Autonomic nervous system dysfunction; COVID-19 pathophysiology; Chronic inflammation; Diagnostic biomarkers; Dysbiosis; Gastrointestinal symptoms; Gut microbiome; Gut-brain axis; Immune dysregulation; Long COVID; Microvascular damage; Neuropsychiatric symptoms; Personalized medicine; Post COVID; Post-Acute Sequelae of SARS-CoV-2 Infection (PASC); SARS-CoV-2 antigen persistence.